Composition, form of production and packaging
Long-acting tablets coated with a film coat of brownish-violet color, round, biconvex, with a matte or slightly shiny surface, odorless or with a weak characteristic odor; on the fracture - yellow with a narrow strip of brownish-violet at the edges.
nifedipine 20 mg
Auxiliary substances: microcrystalline cellulose - 99 mg, lactose monohydrate - 30 mg, croscarmellose sodium - 26 mg, copolymer of methyl methacrylate and ethyl acrylate [1: 2] - 1.9 mg, talc - 2 mg, magnesium stearate - 0.6 mg, giprolose - 0.5 mg.
The composition of the membrane: hypromellose - 5.26 mg, titanium dioxide - 1.64 mg, iron oxide red (E172) - 0.48 mg, ferric iron oxide black (E172) 0.12 mg, magnesium stearate 0.5 mg.
30 pcs. - banks of dark glass (1) - packs of cardboard.
60 pcs. - banks of dark glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
Selective blocker of slow calcium channels, derivative of 1,4-dihydropyridine. Has antihypertensive and antianginal action.
Nifedipine reduces the current of extracellular calcium ions into the cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. Disintegrates the processes of excitation and contraction in the smooth muscles of vessels mediated by calmodulin. In therapeutic doses normalizes the transmembrane current of calcium ions, disrupted in a number of pathological conditions, especially in hypertension. Reduces spasm and dilates coronary and peripheral arterial vessels, reduces OPSS, reduces afterload and myocardial oxygen demand. At the same time it improves the blood supply of the ischemic zones of the myocardium without the development of the syndrome of "stealing", and also increases the number of functioning collaterals.
Nifedipine has virtually no effect on the sinoatrial and AV nodes and does not have antiarrhythmic effects. Does not affect the tone of the veins. Nifedipine increases renal blood flow, causing a mild sodium naresis. In high doses, it inhibits the release of calcium ions from intracellular stores. Reduces the number of functioning calcium channels, without affecting the time of their activation, inactivation and recovery.
When ingested quickly and almost completely (90%) is absorbed from the digestive tract. Bioavailability is 40-60%. Eating increases bioavailability. Exposed to the effect of "first passage" through the liver.
After ingestion 1 tablet. prolonged action of 20 mg therapeutic concentration of nifedipine in blood plasma is achieved after 1 hour and remains at a constant level up to 6 hours (plateau prolonged action), and in the next 30-36 h gradually decreases.
Binding to plasma proteins (albumins) is 94-97%. Penetrates through the BBB and placental barrier, excreted in breast milk. Do not cumulate.
Nifedipine is extensively metabolized in the liver with the formation of 3 metabolites that do not have pharmacological activity.
T 1/2 - 3.8-16.9 h.
60-80% of the dose taken internally is excreted in the urine in the form of inactive metabolites, the rest - with bile and feces.
Pharmacokinetics in specific patient groups
In patients with hepatic insufficiency, the overall clearance decreases and T 1/2 of nifedipine increases.
Chronic renal failure, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics of nifedipine.
- arterial hypertension;
- IHD: for the prevention of seizures with various forms of angina, incl. angiospastic (stenocardia of Prinzmetal);
- Raynaud's syndrome.
The drug is taken orally. Tablets should be swallowed whole, not liquid, squeezed with a small amount of water.
The recommended initial dose of the drug is 1 tablet. (20 mg) 2 times / day. If necessary, the daily dose can be increased to 2 tab. 2 times / day. The maximum daily dose of nifedipine should not exceed 120 mg. It is recommended to divide the daily dose into 2 doses with 12-hour intervals.
In patients with impaired liver function, the drug is used with caution under the control of liver function, with severe violations of liver function, it is necessary to reduce the dose.
In patients with impaired renal function, dose adjustment is not required.
In elderly patients, the metabolism of nifedipine is reduced in the "first pass" through the liver, and the likelihood of worsening cerebral blood flow is also increased because of the possible sharp peripheral vasodilation, therefore, at the beginning of treatment, the dose of Cordaflex В® is reduced approximately 2-fold.
The drug should be discontinued gradually, especially after use in high doses.
The frequency of side effects is brought into line with the following categories: very often (? 1/10); often (? 1/100 - <1/10); infrequently (? 1/1000 - <1/100); rarely (? 1/10 000 - <1/1000); very rarely (<1/10 000); unknown (it is impossible to set the frequency according to available data).
From the nervous system: often - dizziness, headache, drowsiness; infrequently - insomnia, anxiety, paresthesia, dizziness, rarely - hypoesthesia, tremor, sleep disturbances, mood changes.
From the side of the organ of vision: rarely - visual impairment, pain in the eyes.
From the cardiovascular system: often - a feeling of palpitations, symptoms of vasodilation (redness of the face, heat sensation), swelling; infrequent - fainting, tachycardia, marked decrease in blood pressure, orthostatic hypotension; very rarely - in some cases, myocardial infarction may develop, although this is most likely a consequence of the underlying disease.
From the respiratory system: infrequently - shortness of breath; rarely - epistaxis; very rarely - allergic reactions with swelling of the vocal cords, in extreme cases, bronchospasm with life-threatening dyspnea, which appears after the cessation of treatment.
From the digestive tract: infrequent - diarrhea, dryness of the oral mucosa, bloating, nausea, constipation; rarely - vomiting, anorexia, belching, gingivitis, hypertrophic gingivitis; very rarely - esophagitis, intestinal obstruction, ulcerative lesions of the intestine.
On the part of the liver and bile ducts: rarely - a violation of liver function (increase in GGT), very rarely - jaundice, hepatitis.
From the hemopoietic system: very rarely - anemia, leukopenia, thrombocytopenia or thrombocytopenic purpura, agranulocytosis.
From the endocrine system: very rarely - transient hyperglycemia.
From the genitourinary system: infrequently - nocturia, polyuria; rarely - dysuria, impotence; very rarely - there may be a temporary worsening of kidney function on the background of taking nifedipine in patients with renal insufficiency.
From the skin and subcutaneous tissues: often - redness of the skin of the face, accompanied by a feeling of heat; infrequently - itching, skin rash; rarely - angioedema, maculopapular, pustular, vesicular and bullous rash, edema, urticaria; very rarely - hypersensitivity reactions, exfoliative dermatitis may occur. Photodermatitis may occur under the influence of sunlight or ultraviolet light.
From the musculoskeletal system: myalgia, rarely - pain in the joints and muscles, very rarely - arthritis.
Other: infrequently - pain (in the abdomen, in the chest, in the legs), weakness; rarely - allergic reactions, chest pain, chills, fever, gynecomastia (especially in elderly patients and long-term use of the drug - the condition is always normal after discontinuation of treatment), lack of cardiac sphincter, joint swelling, muscle cramps.
Attacks of angina pectoris may appear at the very beginning of therapy, or in patients with a history of angina pectoris - the frequency, duration and severity of attacks may increase. With hypertension or coronary artery disease, sudden withdrawal of nifedipine may trigger a hypertensive crisis or myocardial ischemia (withdrawal syndrome).
- Acute myocardial infarction (in the first 4 weeks);
- cardiogenic shock;
- severe arterial hypotension (systolic blood pressure below 90 mm Hg);
- pronounced aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy (risk of pronounced blood pressure lowering);
- chronic heart failure IV functional class by NYHA;
- simultaneous application of rifampicin;
- pregnancy up to 20 weeks;
- the period of lactation (breastfeeding);
- children and adolescence under 18;
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (the preparation contains lactose monohydrate);
- hypersensitivity to nifedipine and other components of the drug;
- hypersensitivity to other dihydropyridine derivatives.
The drug should not be used to stop attacks of angina pectoris.
Caudaflex В® should be used with caution in patients with chronic heart failure, severe liver and / or kidney dysfunction, severe cerebral circulation disorders, diabetes mellitus, malignant hypertension, bradycardia, hemodialysis patients (due to the risk of severe arterial hypotension) .
PREGNANCY AND LACTATION
Cordaflex В® tablets prolonged action is contraindicated for use until the 20th week of pregnancy.
Controlled studies of the use of the drug Cordaflex В® in pregnant women have not been conducted. According to available clinical data, it is impossible to judge the specific prenatal risk. At the same time, there are data on the increase in the probability of perinatal asphyxia, cesarean section, premature birth and intrauterine growth retardation. It is unclear whether these cases are due to a major illness (arterial hypertension), treatment or a specific effect of nifedipine. The information available is insufficient to exclude the possibility of side effects, which are dangerous for the fetus and the newborn. Therefore, the use of Cordaflex В® after the 20th week of pregnancy requires a careful individual assessment of the risk-benefit relationship for the patient, fetus and / or newborn and can only be considered if other methods of therapy are contraindicated or ineffective.
Careful monitoring of blood pressure in pregnant women should be performed with Kordaflex В® simultaneously with iv administration of magnesium sulfate due to the possibility of excessive blood pressure lowering, which is dangerous for both the mother and fetus and / or the newborn.
Because nifedipine is excreted in breast milk, you should refrain from prescribing Cordaflex В® during lactation, or stop breastfeeding during treatment with the drug.
APPLICATION FOR FUNCTIONS OF THE LIVER
Caudaflex В® should be used with caution in cases of severe renal dysfunction.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired liver function, the drug is used with caution under the control of liver function, with severe violations of liver function, it is necessary to reduce the dose.
APPLICATION FOR CHILDREN
Due to the lack of sufficient clinical data, the drug is contraindicated in children and adolescents under the age of 18 years .
APPLICATION IN ELDERLY PATIENTS
Caution should be exercised in elderly patients due to the highest likelihood of age-related renal dysfunction. At the beginning of treatment, the dose of Kordaflex В® isreduced approximately 2-fold.
Do not use to stop an angina attack.
Particular caution is necessary when prescribing Cordaflex В® to patients with significant arterial hypotension (systolic blood pressure below 90 mmHg). The antihypertensive effect of the drug Cordaflex В® is enhanced with hypovolemia. In case of kidney diseases, the dose of nifedipine should not be adjusted. Decreased pressure in the pulmonary artery and hypovolemia after dialysis can enhance the effects of the drug Cordaflex В® , in connection with which it is recommended to reduce its dose.
Despite the absence of the Coadaflex В® withdrawal syndrome, a gradual reduction in doses is recommended before discontinuation of treatment.
It is important that the regularity of treatment is independent of the state of health, since the patient may not feel the symptoms of hypertension.
Simultaneous prescribing of beta-blockers should be carried out in conditions of careful medical control, as this can lead to excessive reduction of blood pressure, and in some cases - aggravation of the phenomena of heart failure. It is not recommended to simultaneously perform IV therapy with blockers of? -adrenoceptors and intracoronary administration of nifedipine.
During treatment, positive results are possible with a direct Coombs reaction and laboratory tests for antinuclear antibodies.
If during the therapy the patient is required to undergo surgery under general anesthesia, it is necessary to inform the anesthetist about the nature of the therapy.
Caution should be exercised in elderly patients due to the highest likelihood of age-related renal dysfunction.
Care should be taken when using Cordaflex В® in patients with liver disease. With portal hypertension and cirrhosis, the dose should be reduced.
In rare cases, at the beginning of a course of treatment with nifedipine or with an increase in its dose, pain in the chest (angina due to paradoxical ischemia) may occur soon after taking the drug. If there is a causal relationship between the use of Kordaflex В® and angina pectoris, the drug should be discontinued.
Patients with diabetes mellitus need careful medical supervision during the application of the drug Cordaflex В® .
During the course of treatment, the drug should avoid drinking alcohol.
Each tablet contains 30 mg lactose monohydrate, so the drug should not be prescribed to patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.
Symptoms: depending on the severity of intoxication, a marked decrease in blood pressure, tachycardia, chest pain, fainting and unconsciousness due to cardiac arrhythmias (sinus node depression, bradycardia, AV conduction elongation, ventricular extrasystole), oppression of insulin secretion. In more severe cases, there may be confusion, passing into a coma, hyperkalemia, metabolic acidosis, hypoxia and cardiogenic shock with pulmonary edema.
Treatment: there is no specific antidote, therefore, first of all, measures should be taken to remove nifedipine and maintain the function of the cardiovascular system.In case of an overdose, as a first therapeutic measure, gastric lavage should be performed, activated charcoal intake; if necessary, with washing the large intestine.
The complete removal of unabsorbed nifedipine by washing the stomach and colon is especially important in case of overdose with sustained-release preparations in order to prevent further absorption. You can prescribe laxatives, however, in the case of slow calcium channel blockers, one should take into account the inhibition of intestinal peristalsis down to atony. Nifedipine is not excreted by dialysis, therefore hemodialysis is ineffective, but plasmapheresis is recommended (given the high percentage of binding of nifedipine to plasma proteins and a relatively small V d ). As an symptomatic treatment for bradycardia, atropine and / or beta-adrenomimetics may be prescribed. In the life-threatening bradycardia, a temporary pacemaker should be installed. With a marked decrease in blood pressure due to cardiogenic shock and vasodilation of the arteries, calcium (1-2 g calcium gluconate IV), dopamine (maximum 25 Ојg / kg body weight / min), dobutamine (maximum 15 Ојg / kg body weight / min ) and epinephrine or norepinephrine. The dose of these drugs should be determined in accordance with the patient's response. The calcium content in the serum can be normal or slightly elevated. Additional fluid administration should be performed with caution under the control of hemodynamic parameters to prevent cardiac overload.
Rifampicin is a powerful inducer of the isoenzyme CYP3A4. With simultaneous use with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness decreases. The use of nifedipine in conjunction with rifampicin is contraindicated.
Because rifampicin and phenytoin, by induction of the enzyme, significantly reduce the concentration of nifedipine in the plasma, it is impossible to exclude the similar effects of barbiturates and carbamazepine.
With simultaneous administration with other antihypertensive drugs (ACE inhibitors, diuretics, etc.), nitrates, psychotropic medications and preparations containing magnesium, the hypotensive effect may increase.
Simultaneous use with beta-adrenoblockers promotes intensification of antihypertensive and anti-anginal effects, which is generally favorable, however, the use of this combination of drugs requires special care because of the possibility of excessive reduction in blood pressure, development of arterial hypotension and heart failure.
When combined with prazosin, pronounced orthostatic hypotension may occur.
The combined use of nifedipine with digoxin can lead to an increase in the concentration of digoxin in the plasma.
With simultaneous application with theophylline, the concentration of theophylline in plasma can increase.
The use of nifedipine concomitantly with quinidine requires extreme caution, since concomitant administration of quinidine in the plasma may decrease, and with the withdrawal of nifedipine - increase. Simultaneous administration of these drugs can lead to the occurrence of malignant ventricular arrhythmia (pathological increase in the QT interval on the ECG).
Diltiazem increases the concentration of nifedipine in plasma.
Nifedipine may increase the anticoagulant effect of coumarin derivatives.
Since nifedipine is metabolized by the isoenzyme CYP3A4, then any inhibitor or inducer of the enzyme may alter the metabolism of nifedipine: grapefruit juice, erythromycin, antifungal agents from the group of azoles (e.g., ketoconazole), certain fluoroquinolones, norfloxacin, ciprofloxacin, oral contraceptives containing a progestin and HIV protease inhibitors (e.g., indinavir, ritonavir) may inhibit the metabolism of nifedipine and increase its effect. Likewise, simultaneous nifedipine and cimetidine increases its concentration in blood plasma and, thus, the effect of nifedipine, but co-administration of ranitidine does not significantly increase the level of nifedipine in the plasma. Cyclosporin is also a substrate for the isoenzyme CYP3A4, therefore,while admission may increase the duration of action of both drugs. Simultaneous administration of nifedipine with weak and moderate inhibitors of CYP3A4 isozyme requires regular monitoring of blood pressure and the need to reduce the dose of nifedipine. Such drugs include macrolide antibiotics (azithromycin, belonging to the group of macrolides, not an inhibitor of isozyme CYP3A4).
Nifedipine reduces the excretion of vincristine, thus amplifying its side effects. The need to decrease the dose of vincristine should be considered.
Simultaneous administration of cisapride and nifedipine may lead to increased concentrations of nifedipine in the blood plasma. Blood pressure should be monitored and, if necessary, reduce the dose of nifedipine.
Simultaneous application reception quinupristin / dalfopristin and nifedipine may lead to increased concentrations of nifedipine in the blood plasma. Blood pressure should be monitored and, if necessary, reduce the dose of nifedipine.
Clinical studies of the interaction is not performed nifedipine with valproic acid. Since it has been shown that valproic acid increases the concentration in plasma is structurally similar to nifedipine, nimodipine BCCI by inhibiting microsomal liver enzymes, it is impossible to exclude the possibility of increasing concentrations of nifedipine in the blood plasma.
No effect on the pharmacokinetics of nifedipine following medicines: ajmaline, benazepril, debrizohin, doxazosin, irbesartan, omeprazole, orlistat, pantoprazole, ranitidine, rosiglitazone, talinolol, triamterene / hydrochlorothiazide, acetylsalicylic acid and candesartan.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 5 years.